6L70

Complex structure of PEDV 3CLpro with GC376

Summary for 6L70

• Entry DOI: 10.2210/pdb6l70/pdb
• Descriptor: PEDV main protease, (1S,2S)-2-({N-[(benzyloxy)carbonyl]-L-leucyl}amino)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid (3 entities in total)
• Functional Keywords: 3c-like protease, complex, hydrolase
• Biological source: Porcine epidemic diarrhea virus
• Total number of polymer chains: 2
• Total formula weight: 67562.38

Authors

Ye, G.,Peng, G.Q. (deposition date: 2019-10-30, release date: 2020-04-29, Last modification date: 2024-11-13)

Primary citation

Ye, G.,Wang, X.,Tong, X.,Shi, Y.,Fu, Z.F.,Peng, G.
Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376.
Viruses, 12:-, 2020

PubMed Abstract: Porcine epidemic diarrhea virus (PEDV), being highly virulent and contagious in piglets, has caused significant damage to the pork industries of many countries worldwide. There are no commercial drugs targeting coronaviruses (CoVs), and few studies on anti-PEDV inhibitors. The coronavirus 3C-like protease (3CL) has a conserved structure and catalytic mechanism and plays a key role during viral polyprotein processing, thus serving as an appealing antiviral drug target. Here, we report the anti-PEDV effect of the broad-spectrum inhibitor GC376 (targeting 3Cpro or 3CL of viruses in the picornavirus-like supercluster). GC376 was highly effective against the PEDV 3CL and exerted similar inhibitory effects on two PEDV strains. Furthermore, the structure of the PEDV 3CL in complex with GC376 was determined at 1.65 Å. We elucidated structural details and analyzed the differences between GC376 binding with the PEDV 3CL and GC376 binding with the transmissible gastroenteritis virus (TGEV) 3CL. Finally, we explored the substrate specificity of PEDV 3CL at the P2 site and analyzed the effects of Leu group modification in GC376 on inhibiting PEDV infection. This study helps us to understand better the PEDV 3CL substrate specificity, providing information on the optimization of GC376 for development as an antiviral therapeutic against coronaviruses.

PubMed: 32098094
DOI: 10.3390/v12020240

Experimental method

X-RAY DIFFRACTION (1.56 Å)